S-1 and Bevacizumab in Treating Patients With Colorectal Cancer That is Recurrent or Cannot Be Removed by Surgery

Phase II Study of Combination Chemotherapy With S-1 Plus Avastin in Unresectable or Recurrent Colorectal Cancer After Failure of Prior Chemotherapy, Including Irinotecan and Oxaliplatin Regimens.

RATIONALE: Drugs used in chemotherapy, such as S-1, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving S-1 together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving S-1 together with bevacizumab works as third-line therapy in treating patients with colorectal cancer that is recurrent or that cannot be removed by surgery.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: bevacizumab; Drug: tegafur-gimeracil-oteracil potassium

Detailed Description

OBJECTIVES:

• To evaluate giving S-1 with bevacizumab to see how well it works as third-line therapy in KRAS-mutation patients with unresectable or recurrent colorectal cancer.

OUTLINE: Patients receive oral S-1 twice daily on days 1-28 and bevacizumab IV on days 1, 15, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Osaka
    • Takatsuki, Osaka, Japan, 569-8686
      • Recruiting
      • Osaka Medical College
      • Contact: Hiroya Takiuchi, MD, PhD; Phone Number: 81-72-683-1221

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal carcinoma

  • Inoperable, locally advanced, or metastatic disease
  • KRAS-mutated
• Concurrently receiving treatment containing irinotecan and oxaliplatin regimens for unresectable or recurrent colorectal cancer
• Measurable disease according to RECIST
• No moderate or severe ascites or pleural effusion requiring treatment
• No metastasis to the CNS

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• White blood cell count > 3,500/mm³ but < 12,000/mm³
• Neutrophil count > 1,500/mm³
• Hemoglobin > 9.0 g/dL
• Platelet count > 100,000/mm³
• Total bilirubin < 1.5 mg/dL
• AST and ALT < 100 U/L (< 200 U/L in patients with liver metastasis)
• Serum creatinine < 1.2 mg/dL
• Creatinine clearance ≥ 50 mL/min
• Urine dipstick for proteinuria < 1+
• INR < 1.5
• Not pregnant or nursing
• Able to take capsules orally
• No active second cancer
• No active infections (e.g., patients with pyrexia of ≥ 38°C)
• No serious complications (e.g., pulmonary fibrosis, interstitial pneumonitis, heart failure, renal failure, hepatic failure, poorly controlled diabetes, or hypertension)
• No electrocardiographic abnormalities with cardiac disorder that would clinically preclude the execution of the study as judged by the investigator
• No serious drug hypersensitivity or a history of drug allergy
• No thrombosis, cerebral infarction, myocardial infarction, or pulmonary embolism
• No history or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
• No clinically significant traumatic injury within the past 4 weeks
• No severe mental disorder

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Concurrent low-dose aspirin therapy (< 325 mg/day) allowed
• More than 4 weeks since prior major surgical procedure or open biopsy
• No prior therapy radiotherapy
• No prior therapy with S-1
• No prior chemotherapy include irinotecan and oxaliplatin as first- or second-line treatment.
• No concurrent continuous treatment with steroids
• No concurrent treatment with flucytosine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Disease-control rate

Secondary Outcome Measures

Outcome Measure
Response rate
Progression-free survival
Overall survival
Safety

Collaborators and Investigators

• Sponsor: Osaka Medical College
• Investigators: Principal Investigator: Hiroya Takiuchi, MD, PhD, Osaka Medical College

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Anticipated): June 1, 2010

Study Registration Dates

• First Submitted: September 9, 2009
• First Submitted That Met QC Criteria: September 9, 2009
• First Posted (Estimate): September 10, 2009

Study Record Updates

• Last Update Posted (Estimate): August 12, 2013
• Last Update Submitted That Met QC Criteria: August 9, 2013
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer; stage III colon cancer; stage III rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Tegafur
• Other Study ID Numbers: OSAKA-TRICC0901; CDR0000649021 (Registry Identifier: PDQ (Physician Data Query))